BACKGROUND: The effect of human papillomavirus (HPV) vaccination on cervical intraepithelial neoplasia grade 2 or worse (CIN2+) recurrence with respect to cone margin positivity is unknown. Most studies assessed this effect beyond two months post-conisation. We aimed to determine both the duration and early onset of effect in women who had been prophylactically vaccinated or vaccinated after conisation, considering cone margin status. METHODS: This cohort study used data from one of the central laboratories in the Czech Republic, covering approximately 33% of women undergoing national cervical cancer screening. It included women treated for CIN2+ between 2010 and 2024 who had received either prophylactic HPV vaccination (available through the national immunisation program since 2011) or post-conisation vaccination (recommended by the Czech Gynaecological and Obstetrical Society since 2008). The vaccination effect was estimated using the incidence rate ratio (IRR) from a Poisson regression model, calculated as 100 × (1-IRR). FINDINGS: Of the 10,054 women enrolled, 919 were vaccinated after conisation, 502 prophylactically, and 169 had undetermined timing of vaccination. Throughout the follow-up period, CIN2+ recurrence was observed in 513 unvaccinated women, with a rate of 14·61 per 1000 person-years (py), in 14 prophylactically vaccinated women, with a rate of 5·84 (54% reduction; 95% confidence interval [CI]: 22-73%), and in 15 women vaccinated post-excision, with a rate of 3·37 (74% reduction; 95% CI: 57-85%). The high recurrence rate of 58·59 per 1000 py within six months of conisation was reduced by 80% (95% CI: 19-95%) with prophylactic vaccination and by 89% (95% CI: 57-97%) with incomplete post-excision vaccination. Among a total of 1771 women with a positive cone margin, recurrence was identified in 272 of 1568 unvaccinated women, corresponding to a recurrence rate of 51·62 per 1000 py. A reduction was observed in 84 prophylactically vaccinated and in 119 women vaccinated post-excision, with only 6 recurrence cases documented in each group. This corresponded to recurrence rates of 14·94 (62% reduction; 95% CI: 14-83%) and 9·78 per 1000 py (79% reduction; 95% CI: 52-90%), respectively. INTERPRETATION: Regardless of timing, HPV vaccination has a beneficial long-term effect in lowering the risk of CIN2+ recurrence. Despite the greater reduction in relapse achieved by post-excision vaccination, the difference compared with the prophylactic one was not statistically significant. The most pronounced benefit was observed within the first six months post-conisation, particularly in women with a positive cone margin. FUNDING: Cooperatio 31 fund, Health Sciences, Charles University, Prague, Czech Republic.

Centre of Ambulatory Gynaecology and Primary Care Brno 602 00 Czech Republic

Department of Anaesthesia and Intensive Medicine 1st Faculty of Medicine Charles University and University Military Hospital Prague 100 00 Czech Republic

Department of Epidemiology and Biostatistics 3rd Faculty of Medicine Charles University Prague 100 00 Czech Republic

Department of Health Care and Population Protection Faculty of Biomedical Engineering Czech Technical University Prague Kladno 272 01 Czech Republic

Department of Hygiene 3rd Faculty of Medicine Charles University Prague 100 00 Czech Republic

Department of Medical Biophysics and Informatics 3rd Faculty of Medicine Charles University Prague 100 00 Czech Republic

Department of Obstetrics and Gynaecology Palacký University Olomouc Faculty of Medicine and Dentistry University Hospital Olomouc Olomouc 775 15 Czech Republic

Královské Vinohrady University Hospital Prague 100 00 Czech Republic

Laboratory for Atherosclerosis Research Centre for Experimental Medicine Institute for Clinical and Experimental Medicine Prague 140 21 Czech Republic

Unilabs Pathology k s Prague 160 00 Czech Republic

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